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Background: The prevalence of significant liver disease in persons with asymptomatic hepatitis C virus (HCV) infection is unclear. Objective: To determine the prevalence and severity of HCV infection in asymptomatic persons. Design: Population-based cross-sectional study. Setting: Northeastern Italy. Patients: 4820 apparently healthy Telecom Italy employees or their relatives who underwent screening for cardiovascular risk factors. Measurements: Initial screening for anti-HCV by enzyme-linked immunosorbent assay followed by HCV RNA testing by polymerase chain reaction and monitoring of alanine aminotransferase levels in viremic persons (92% of viremic persons also had liver biopsies to assess their METAVIR scores). Results: 116 persons (2.4% [95% CI, 1.97% to 2.84%]) were positive for anti-HCV and 85 (1.76% [CI, 1.39% to 2.14%]) were also viremic. The ALT level was persistently normal in 39 (46%) of viremic patients and elevated in 46 (54%). Significant hepatic histologic abnormalities were detected in 19% (CI, 7.21% to 36.4%) of persons with persistently normal ALT levels and in 61% (CI, 45.4% to 74.9%) of viremic persons who had elevated ALT levels (P Conclusions: Hepatitis C is histologically active and progressive in up to 40% of asymptomatic persons with HCV infection. The severity of liver disease correlates with abnormal ALT levels and increases with age.